1. Field of the Invention
The present invention relates to a Th1-specific-protein and a gene encoding the protein. More specifically, the present invention relates to a protein which is specific solely for human Type 1 helper T cells and which can be advantageously used as means for simply and promptly specifying variations in balance among helper T cell subsets intimately involved in immunological disorders, such as atopic diseases or the progression of AIDS. The present invention also relates to a gene which encodes this protein.
Further, the present invention relates to a recombinant vector which harbors the gene and is used for expressing it, as well as to a transformant which is transformed with the recombinant vector.
Furthermore, the present invention relates to polyclonal and monoclonal antibodies against the Th1-specific protein, and a hybridoma which produces the monoclonal antibody.
2. Description of the Related Art
Immunology has made a remarkable progress in recent years and has added a great contribution to various fields of medicine.
Studies of immunology have revealed that cytokines produced by macrophages or lymphocytes play the central role in promoting or suppressing every immunological reaction, such as infection immunity, tumor immunity, allergies, or anaphylaxis.
Mosmann and Coffman, et al. classified CD4.sup.+ T-cell clones which are established from mouse spleen cells and can be cultured for a long period of time into two different types of subsets according to the difference between cytokines produced by the clones (Mosmann, T. R., et al., J. Immunol., 136, 2348 (1986)).
Specifically, they classified CD4.sup.+ T-cell clones into the "T-helper 1 (Th1) subset" and the "T-helper 2 (Th2) subset": the former principally produces IL-2, IFN (interferon)-.gamma., and TNF (tumor necrosis factor)-.beta.; and the latter principally produces interleukin 4 (IL-4), IL-5, IL-6, IL-10, and IL-13.
Although the existence of such subsets of helper T cells in humans was initially deemed dubious, it is now well accepted (Romagnani, S., Immunology Today 12, 256 (1991), etc.).
Nowadays, the nature and functions of the helper T-cell subsets Th1 and Th2 in mice or humans are becoming much more evident. In terms of biological significance, they have become of great interest as dominant cells which control different immunological reactions.
In many infectious diseases or immunological diseases, polarization is observed in the distribution of the Th1/Th2 subsets of lymphocytes of patients; i.e., an extreme bias arises in the distribution toward either one of the subset Th1 or Th2. Therefore, it is suggested that the nature of this polarization phenomenon may reflect the condition and type of the disease.
For example, the following are currently known: (1) in the case of Mycobacterium diseases, if immunological reactions with respect to Mycobacterium are mainly delayed-type hypersensitivity (DTH) reactions, the Th1 subset is dominant, whereas if the immunological reactions are chronic and progressive, the Th2 subset is dominant. (2) In the case of HIV diseases, the production of Th1-type cytokines is observed among many long-term nonprogressive HIV-infected patients. If polarization arises toward the Th2 subset, the symptoms of the diseases become progressive or fulminated. (3) With regard to patients having atopic diseases, if there arises polarization toward the Th2 subset, the diseases become aggravated.